A. Field of the Invention
This invention relates to the synthesis of acid anhydrides from carboxylic acids and acid halides using solid phase co-polymers as catalysts.
B. Prior Art
Acid anhydrides are among the most important classes of reagents in organic chemistry. They are frequently the preferred reactive acid derivatives for preparation of esters, amides, and peptides. Further, anhydrides of formic acid are potentially very useful formylating agents. However, among the group of anhydrides which may potentially act as formylating agents, only acetic formic anhydride has been used extensively. Symmetrical formic anhydride, the formylating agent of choice, has not often been employed because it is highly unstable and can only be handled at temperatures below -40.degree. C. It readily decomposes to formic acid and carbon monoxide. Moreover, most mixed formic anhydrides are also unstable since they are prone to disproportionation or decomposition particularly in the presence of catalysts used in their synthesis.
In the past, anhydrides most commonly have been synthesized from acid halides (usually the chlorides) and carboxylic acids by means of transacylation reactions. These transacylation reactions utilize nucleophilic catalysts such as pyridine. Acid halides are known to acylate pyridine catalysts forming acylpyridinium intermediates and to acylate other tertiary amines to form acylammonium ions which, in turn, react with carboxylate ions to form the desired anhydride.
Although these amine catalysts are effective in forming anhydrides, their use has several disadvantages. For example, transacylation catalysts often further catalyze the disproportionation of newly formed mixed anhydride products and the decomposition of other unstable anhydride products. Stevens, W. & Van es, A. Recl. Trav. Chim. Pays-Bas. 83: 1287 (1964) and Ibid. 84: 704 (1965). Moreover, additional purification steps are required to separate these catalysts from the product and regenerate them for repeated use. See R. K. Smalley and H. Suschitzky, J. Chem. Soc. 755 (1964).
The simplicity and convenience of processes that use solid-phase polymeric reagent/catalysts has been generally acknowledged. See for example, A. Akelah and D. C. Sherrington, 81 Chem. Rev. 557 (1981); A. Akelah, Synthesis 413 (1981); S. Bowin et al. Bull. Soc. Chim. Fr. II-201 (1984); M. Ralitsch et al. 13 Rev. Latinoam. Quim. 16 (1982) and Y. Shai et al., 107 J. Am. Chem. Soc. 4249 (1985). However only a small number of applications of this methodology to transacylation reactions have been reported. No application of a polymeric catalyst/reagent to anhydride synthesis has ever been reported.
Accordingly, it is an object of the present invention to provide a method of synthesis of anhydrides using solid-phase polymeric catalysts and soluble polymeric catalysts in single and mixed solvent systems.
It is another object of the present invention to provide solid phase and soluble polymeric catalysts which do not degrade or disproportionate the anhydride products.
It is a further object of the present invention to provide a method for synthesizing stable anhydrides of formic acid.